Several intraocular diseases and conditions of the eye threaten vision. Age related macular degeneration (ARMD), choroidal neovascularization (CNV), retinopathies (e.g., diabetic retinopathy, vitreoretinopathy), retinitis (e.g., cytomegalovirus (CMV) retinitis), uveitis, macular edema, ocular tumors, and glaucoma are several examples.
Age related macular degeneration (ARMD) is the leading cause of blindness in the elderly in the United States. ARMD attacks the center region of the retina 214 (i.e., macula), responsible for detailed vision and damages it, making reading, driving, recognizing faces and other detailed tasks difficult or impossible. Current estimates reveal that approximately forty percent of the population over age 75, and approximately twenty percent of the population over age 60, suffer from some degree of macular degeneration. “Wet” or exudative ARMD (e.g., WAMD) is the type of ARMD that most often causes blindness. In wet ARMD (e.g., WAMD), newly formed choroidal blood vessels (choroidal neovascularization (CNV)) leak fluid and cause progressive damage to the retina. It is estimated that about 15% of all cases of ARMD are of the wet type (WAMD).
Ocular tumors may be primary or secondary. Examples include but are not limited to ciliary body melanomas, choroidal melanomas, hemangiomas, and metastatic tumors. Intraocular tumors can cause blindness or death through direct disruption of tissues or metastatic spread.
Treatment of WAMD has traditionally consisted of thermal laser photocoagulation of the abnormal neovascular membrane. A drawback of laser photocoagulation is that the laser ablates all structures in its path, not just the abnormal vessels but also the normal retina and choroid, resulting in vision loss at the location of laser application. When this treatment is applied to subfoveal membranes (membranes located below the fovea 210, the very center of the macula), the result is an immediate, permanent, severe central vision loss.
More recently, Photodynamic Therapy (PDT) has been applied to subfoveal membranes. In PDT therapy, a photosensitizing (light activated) dye is injected into the patient's bloodstream. A non-thermal (non-burning) laser is applied to the neovascular membrane 212. The dye is activated at the site of the laser application resulting in localized damage to the neovascular membranes. The result is localized damage to the young, abnormal, photosensitized vessels but not the normal vessels and retina tissue. While PDT has yielded better visual results than thermal photocoagulation or observation alone (e.g., no treatment) it does not usually lead to an improvement of vision.
Currently, a standard of practice treatment of WAMD consists of serial intraocular injections of a Vascular Endothelial Growth Factor inhibitor (anti-VEGF), e.g., bevacizumab, ranibizumab, injected directly into the vitreous gel. Anti-VEGF treatment has proven to be the only treatment to date that significantly stabilizes and often improves vision. A drawback of anti-VEGF therapy is a relatively short duration of action, requiring monthly injections. Numerous injections are required with concomitant discomfort and repeated exposure to small but not negligible risks of complications such as infection, inflammation, bleeding, and retinal detachment. A limitation of anti-VEGF treatment is a limited effect of anti-VEGF agents against developed choroidal neovascular membranes (CNVMs). For example, CNVMs are stabilized by anti-VEGF agents, but are not necessarily eliminated. In some cases, cessation of monthly injections of anti-VEGF agents can cause a gradual decline in vision as the CNVMs are reactivated.
Intraocular tumors such as melanomas may be treated with external beam radiation therapy, brachytherapy, and/or with chemotherapy, the goal of the therapies being to selectively damage reproducing cells. External beam radiation therapy disrupts the reproducing cells (e.g., tumor cells) and can cause regression of the tumor. However, the high-energy radiation used with external beam radiation therapy has the potential risk to induce radiation retinopathy, which may cause long-term retinal vascular damage and/or decreased vision. Chemotherapy may be applied via systemic administration of through injections into ocular tissues.
Brachytherapy is treatment of a region by placing radioactive isotopes in, on, or near it. Compared to external beam radiation therapy, brachytherapy uses a small, less powerful radiation source placed in close proximity to the tumor, which limits the radiation exposure to surrounding tissues. The Collaborative Ocular Melanoma Study (COMS), a multicenter randomized trial sponsored by the National Eye Institute and the National Cancer Institute, demonstrated the utility of brachytherapy for the treatment of ocular cancers and/or tumors. The technique employs an invasive surgical procedure to allow placement of a surface applicator (called an episcleral plaque) that is applied extraocularly by suturing it to the sclera 208. The gold plaque contains an inner mold into which radioactive iodine 125 (I-125) seeds are inserted. The gold plaque serves to shield the tissues external to the eye while exposing the sclera, choroid, choroidal melanoma, and overlying retina to radiation. The plaque remains fixed for a few days to one week in order to deliver approximately 85 Gy to the tumor apex.
Currently under investigation, brachytherapy treatments for WAMD generally involve performing a pars plana vitrectomy to remove most of the vitreous gel and placing a cannulum containing the radioactive seed 120 in direct contact with the retina overlying the neovascular membrane (NVM). A pars plana vitrectomy presents risks associated with manipulation of the vitreous and placement of a probe on the retinal surface. Risks associated with the procedure include endophthalmitis, retinal detachment, cataract formation, bleeding, glaucoma and mechanical retinal damage (from direct contact) and those of general anesthesia, often required for this type of surgery.
The present invention features methods and devices for delivery of radiation to the posterior portion of the eye (e.g., for WAMD, for ocular tumors, etc.) via a suprachoroidal procedure. A brachytherapy source (e.g., a radioactive seed) is placed in close proximity to a choroidal neovascular membrane (CNVM) via the suprachoroidal space (between the choroid and sclera).
Any feature or combination of features described herein are included within the scope of the present invention provided that the features included in any such combination are not mutually inconsistent as will be apparent from the context, this specification, and the knowledge of one of ordinary skill in the art. Additional advantages and aspects of the present invention are apparent in the following detailed description.